I propose to continue isolation and characterization of the components of the venom from the Brazilian scorpion, Tityus serrulatus that are responsible for inducing exocrine secretory activity in our preliminary studies of the guinea pig pancreas. Stings for this scorpion have been reported to lead to a high incidence of acute pancreatitis in humans. Both biochemical and morphological studies will be carried out using whole venom and its purified components, in vivo and in vitro. The primary structure of the venom protein exocrine pancreatic secretagogues will be determined in order to determine the amino acid sequence responsible for activating the discharge activity. The venom protein secretagogues will be cleaved chemically and enzymatically to short peptides of known sequence. The peptides will be tested for secretagogue activity in an in vitro discharge assay system and compared with other known peptide exocrine pancreatic secretagogues to determine possible sequence homology. We will describe the specific biochemical events in exocrine pancreatic discharge that is stimulated by the scorpion venom secretagogue proteins and any active peptides cleaved from them. Ultrastructural changes induced by the venom and its components in the pancreatic acinar cells will be observed by electron microscopy of tissue samples taken during the biochemical studies. The association between stings from scorpions of the genus Tityus in humans and the subsequent development of pancreatitis forms the basis of our interest in this venom. Both biochemical data and the structural changes observed in this work will be related to the development of an experimental model for pancreatitis and its etiology.